Method and system for measuring pulmonary artery circulation information

ABSTRACT

Minimally invasive systems and methods are described for measuring pulmonary circulation information from the pulmonary arteries. A transbronchial Doppler ultrasound catheter is advanced through the airways and in the vicinity of the pulmonary artery. Doppler ultrasound energy is sent through the airway wall and across the pulmonary artery to obtain velocity information of blood flowing through the artery. The velocity information is used to compute pulmonary circulation information including but not limited to flowrate.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a Continuation of Ser. No. 12/272,703 filedNov. 17, 2008 (Allowed), which application claims the benefit under 35USC 119(e) of U.S. Provisional Application No. 60/988,738 filed Nov. 16,2007. The full disclosures, each of which are incorporated herein byreference in their entirety for all purposes.

BACKGROUND OF THE INVENTION

It is well established that assessing pulmonary arterial pressure (PAP)is useful in diagnosing pulmonary disease such as pulmonaryhypertension. PAP, however, may remain relatively unchanged followingclinical treatment to address pulmonary hypertension. Thus, while usefulas an indicator of the presence of pulmonary disease, PAP alone may notbe practical for evaluating improvement and patient response totreatment. For this reason, additional pulmonary circulation informationis desired.

Total pulmonary vascular resistance (TPR) provides information about theflowrate and pressure in the pulmonary vasculature. TPR is a ratio ofthe PAP to flowrate. Unlike PAP, TPR changes to some degree in responseto treatment and can therefore be used to help assess the efficacy ordegree of the treatment effect that eventually results in patientimprovement.

Various approaches are available to obtain pulmonary information. Forexample, a passive approach is disclosed in Patent Pub. No. 2001/0039383to Mohler. In this application, a sensor assembly is provided thatdetects heart sounds. The sensor is placed in contact with the skin, andis connected with a signal processing means. Pressure information ismeasured based on acoustic wave signatures arising from the heart. Seealso U.S. Pat. No. 6,368,283 to Xu et al.

A more invasive approach involves implanting a medical device forsensing the absolute and barometric pressures as disclosed in U.S. Pat.No. 6,024,704 to Meador et al. The implantable sensor described inMeador includes two leads. One lead is positioned in the subcutaneouslayer of the skin for measuring the barometric pressure and a secondlead is positioned in the right ventricle of the heart for measuringpressure therein. The contents of the above teachings are incorporatedby reference in their entirety and may be optionally combined with themethods and devices described herein.

Despite the results of the above mentioned measurement techniques, aninvasive catheterization procedure is still considered by manyphysicians to be the gold standard to confirm pulmonary hypertension andfor determining the PAP. In a right heart catheterization, a catheter isinserted through the pulmonary arteries and into the right ventricle ofthe heart. Once positioned in the right ventricle, the pulmonarypressure is measured directly using a pressure sensor. However, thisprocedure requires penetration of the vasculature, and requiressignificant surgical intervention. As such, the procedure carries anundesirable amount of inconvenience, cost, and risk to the patient.

A more convenient, less invasive approach is desired for obtainingaccurate pulmonary circulation information.

SUMMARY OF THE INVENTION

Minimally invasive systems and methods are described for measuringpulmonary circulation information from the pulmonary arteries.

Variations of the medical systems for measuring pulmonary circulationinformation of the pulmonary artery include a catheter comprising atleast one ultrasonic transducer, and an ultrasound Doppler signalprocessing unit for processing signals sent by and received from thetransducer. The system can also include a processor or processor meansfor analyzing the Doppler signals to perform the analysis of thepulmonary circulation information disclosed herein. In such a case, theprocessor or processor means can include a typical microprocessor baseddevice that is either discrete from or integral with the Doppler signalprocessing unit. The system can also include a visual indicator. Thevisual indicator can be located on either the face of the control unitor the processor. Alternatively, or in combination, the visual indicatorcan transmit signals to another monitor (such as those used with abronchoscope) so that information can be displayed on the monitor andobserved by the physician during the procedure.

In one variation, the system includes catheters having designs suitedfor obtaining anatomic information or arterial flow related information.For example, a number of transducers may be located at various angleswith respect to an axis of the catheter. In another variation, thetransducer(s) can rotate or move within the catheter.

The system can also include a data set of predetermined waveformsobtained by and associated with direct measurement of pulmonary arterialpressure. The data set is used to compare a real-time or other measuredpressure signature to one or more of the predetermined waveforms todetermine an estimated mean arterial pressure or other pulmonarycirculation information. This predetermined data set can be storedwithin memory means that is integrated with the controller or processor.Alternatively, the data set can be provided to the system via aremovable means of data storage. Examples of such memory means arecommonly known.

The present invention also includes methods for determining pulmonarycirculation information in a pulmonary artery without puncturing oropening the pulmonary artery. The methods include providing anultrasound Doppler catheter, said catheter comprising a distal sectionand at least one ultrasound transducer in said distal section, advancingsaid distal section of said ultrasound Doppler catheter through anatural respiratory opening, and into an airway and to a location alongan airway wall such that at least a portion of said distal section andsaid at least one ultrasound transducer is in proximity of the pulmonaryartery, sending and receiving ultrasonic waves to said pulmonary arteryfrom said ultrasound transducer; determining a measured pressuresignature by analyzing the received ultrasonic waves, and comparing themeasured pressure signature to one or more predetermined pressuresignatures wherein each of said predetermined pressure signatures has anassociated mean pulmonary arterial pressure.

The present invention also includes a method for determining flowrate ina blood vessel comprising determining velocity profiles across the bloodvessel and computing the flowrate based on said velocity profiles.

The description, objects and advantages of the present invention willbecome apparent from the derailed description to follow, together withthe accompanying drawings. The invention includes any number ofcombination of method and devices, or aspects of such methods anddevices where such combinations are possible.

The disclosure and invention specifically include combination offeatures of various embodiments as well as combinations of the variousembodiments where possible.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of a catheter system in accordance with thepresent invention.

FIG. 2 is an anterior view of a catheter positioned in the bronchi andin the vicinity of a pulmonary artery.

FIG. 3 is an enlarged view of a catheter distal end in accordance withone embodiment of the present invention.

FIG. 4 is an enlarged view of a catheter distal end comprising aplurality of ultrasonic transducers.

FIG. 5 is an enlarged view of a catheter distal end comprising anotherembodiment of the present invention.

FIG. 6 is an illustration of an ultrasound Doppler probe positionedwithin an airway and sending a beam through the airway wall and across ablood vessel.

FIG. 7 is a plot of a velocity profile across a blood vessel as afunction of distance from the Doppler probe in accordance with thepresent invention.

FIG. 8 is an illustration of an ultrasound Doppler probe within anairway and sending a beam through the blood vessel wherein the probe ispositioned at an angle to the blood vessel.

FIG. 9a is an illustration of a tissue region divided into a pluralityof discrete sub-sections.

FIG. 9b is a plot of a velocity profile across the tissue regionillustrated in FIG. 9 a.

FIG. 10 is a plot of velocity profiles measured at different times.

FIG. 11 is a plot of a flowrate calculated over a time duration inaccordance with the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Novel systems and methods to determine pulmonary circulation informationare described herein. In particular, the systems and method can includeminimally invasive approaches to determine pulmonary circulationinformation. In one variation, a transbronchial or bronchoscopicapproach is described that measures pulmonary pressure and volumetricflowrate of the fluid in the pulmonary artery. The described system iscapable of measuring various indicia of pulmonary circulationinformation without the need or requirement to penetrate the arterialwall or otherwise enter the vasculature. In additional variations, thesystems described herein can be combined with conventional measurementmodes for improved assessment of pulmonary circulation.

FIG. 1 illustrates a catheter system in accordance with one embodimentof the present invention. System 10 includes a Doppler ultrasoundcatheter 20 and a signal processing unit 30. The processing unit 30 canalso include a processor or processor means for analyzing the Dopplersignals to perform the analysis of the pulmonary circulation informationdisclosed herein. Alternatively, the processor means may be a separatecomponent. However, such a processor can be incorporated together withthe Doppler processing unit 30.

FIG. 1 also illustrates the processing unit 30 as including a visualindicator 34 or display. In additional variations, the visual indicator34 can comprise a signal generated by the system that causes visualinformation or other data to be displayed on a monitor coupled to thebronchoscope.

The catheter 20 includes a flexible shaft and a distal working endsection. The distal section comprises an ultrasound transducer 40 thatis electrically coupled to the signal processing unit (SPU) 30. As willbe discussed further below, Doppler ultrasound analysis is carried outto identify and determine various attributes of the pulmonary blood flowsuch as flowrate and pressure. However, other non-invasive imaging ormeasurement modalities can be used with the principles of the inventionsuch as, for example, laser Doppler.

One application of the above mentioned system is shown in FIG. 2. Inparticular, the ultrasound catheter 20 extends through the trachea andinto the left bronchi 50. The end of the catheter is shown behind orposterior to the pulmonary artery 60. As shown, the catheter can extendindependently in the airways. However, the present invention may becarried out with the use of a bronchoscope or other guiding sheath,where the catheter may be extended through the bronchoscope or guidingsheath. A bronchoscope provides an additional mechanism to view theprocedure.

FIG. 3 illustrates the distal end section of catheter 20 within bronchi50 and in the vicinity of the pulmonary artery 60. The tip is shown incontact with the airway wall. Once positioned at a location along theairway, and in the vicinity of the pulmonary artery 60, variouscirculation information of the pulmonary artery may be determined suchas, but not limited to: the arterial pressure, blood-flow velocity,arterial diameter and cross-sectional area, blood flowrate, cardiacoutput, and total pulmonary resistance (TPR). The entire blood-flowvelocity waveform in response to right ventricle contraction and fillingmay also be collected.

Pulmonary Arterial Pressure

Pulmonary arterial pressure (PAP) may be determined by varioustechniques including without limitation ultrasound waveform analysis.Ultrasound waveform analysis is carried out by sending and receivingultrasound waves from the ultrasonic transducer 40 and relies on aDoppler Effect measurement to obtain flow-rate waveforms. Themeasurements may occur over a duration of time or over a number of heartbeats. The actual waveform characteristics are then compared to known(or predetermined) waveform information. For example, the waveformcharacteristics of healthy and diseased individuals can be establishedas baselines. In practice, the measured flow pattern is then compared tothe base waveforms of healthy and diseased patients to assess whether aflow pattern indicates pulmonary hypertension.

Method of non-invasively determining pulmonary hypertension by Doppleror other means are discussed in Non-Invasive Evaluation of PulmonaryHypertension by a Pulsed Doppler technique by A. Kitabatake (Circulation1983; 68;302-309). However, these techniques require visualization fromoutside the body. Moreover, such external imaging of COPD patients isdifficult in view of the large amount of air trapped withinhyper-inflated lungs. More direct measuring of characteristics of bloodpressure and assessing pulmonary hypertension from within an airwayunder the present invention overcomes these problems. For COPD patients,the method of the present invention may be used to capture waveformsthat might be unobtainable using the transthoracic technique describedby Kitabatake.

As noted above, the precursor (or actual, or measured) pressuresignature is compared to a set of predetermined (or baseline) waveforms,each of which corresponds to a specific mPAP. The database is preferablycreated by comparing characteristics of collected waveforms to pressuremeasurements obtained by a traditional standard such as the right heartcatheterization. Preferably, the database includes a range ofpredetermined waveforms correlated to mean pulmonary pressures from 10to 80 mmHg, with standard of deviation of 5. If the physician determinestreatment is necessary, the physician can administer the appropriatetreatment (e.g., surgical intervention, drugs, etc.). The physician canthen assess the effects of such treatment by obtaining an additionalpressure or waveform signatures.

A waveform analysis process is further described in commonly assignedProvisional application No. 60/944,730, filed Jun. 18, 2007, andentitled MEASUREMENT OF PULMONARY HYPERTENSION FROM WITHIN THE AIRWAYS,the entirety of which is incorporated by reference.

As indicated above, total pulmonary vascular resistance (TPR) is anotheruseful calculation for the physician. TPR is a ratio of the pulmonaryartery pressure to the cardiac output, namely, volumetric flowrate (Q).Hence, the flowrate must be determined in order to determine TPR.

Pulmonary Arterial Flowrate

Flowrate may be determined using a number of different approaches. Afirst approach obtains flowrate (Q) by determining the velocity, and thecross sectional area, and multiplying the two numbers according to theequationQ=V×A,where A is cross sectional area and V is average velocity within thatcross sectional area.

Velocity (V) may be calculated using Doppler shifting analysis with theDoppler catheter system described above. A series of ultrasound wavesare delivered from transducer 40, reflected off moving objects (namely,blood cells, micro-bubbles, or the like) in the fluid. These reflectedwaves or signals are sampled at a series of intervals corresponding to.round trip transit times between the transducer 40 and the varioussample volumes within the blood vessel. The blood flow velocity of eachsample volume can then be determined by detecting the Doppler frequencyshift of the transmitted signal using well known techniques.

The direction of blood flow can be determined using two referenceultrasound signals that are generated at 90 degrees out of phase witheach other. Utilizing such techniques it is possible to map a onedimensional velocity profile by establishing a number of individualrange gates and spanning the diameter of the blood vessel in which thetransducer is positioned. There are a number of intravascular examplesof this type of measurement such as that described in U.S. Pat. Nos.5,339,816 and 4,856,529 (each of which is incorporated by reference).

The cross-sectional area (A) is proportional to the square of thediameter of the vessel. In particular, A=π×D²/4. Consequently, in thisembodiment of the invention, the diameter (D) or radius is measured orestimated in order to determine A.

The vessel diameter (D) can be determined utilizing automatic diameterdetection system of the type well known to those skilled in the art. Forexample, U.S. Pat. No. 4,856,529 describes a system which providesdynamic range-gating and diameter detection utilizing Doppler shiftedultrasonic power within three sample gates. The gates correspond to onecentered on the distal vessel wall, one near the vessel wall and onewithin the center of the vessel. A feedback loop adjusts gate positionsso that reflected Doppler power from the far wall is a preset fractionof the Doppler power obtained from a sample volume located entirelywithin the central vessel lumen. The vessel diameter is then determinedby continuously detecting the delay transit time to the far sample gateas it is adjusted to remain centered on the far wall. Instantaneous flowis calculated from the instantaneous space average velocity andinstantaneous diameter using formulas well known to those skilled in theart.

Another technique for measuring the diameter is based oil a time offlight analysis and is described in, for example, U.S. Pat. No.5,078,148 to Nassi et al. Still other techniques may be employed tomeasure the diameter and cross-sectional area of the blood vessel andthe invention is intended only to be limited to the appended claims.

One complexity in analyzing the Doppler time of flight data iscompensating for the angle of the ultrasound waves relative to thevessel all or fluid flow. In particular, with reference to FIG. 3, thedirection of propagation of the ultrasound waves may be at an angle (B)to the diameter (D). In the event the ultrasound pulses and wavespropagate through the fluid at an angle (B), the diameter may beestimated larger than its actual value. It is therefore useful toestimate or identify the angle (B) and compensate for an increase ordecrease in measured distances.

One technique for estimating the angle (B) is illustrated in FIG. 3. Thecatheter 20 comprises a single transducer 40. The distal section andtransducer 40 may be extended out of a bronchoscope and articulatedagainst the airway wall at a particular angle such as 0, 45, or 90degrees. In this manner. the angle is ascertained. This angle may beused in combination with the Doppler ultrasound shifting and time offlight information to identify D, A, and V. Alternatively, the catheterdistal end may include a mechanical feature or characteristic thatrepeatably orients the catheter tip at a known angle to blood flow. Forexample, a pre-existing bend in the distal section can necessarily forma certain angle (A) with the vessel wall.

Additionally, a corkscrew shaped distal end, or S-bend shape mayreliably locate the transducer in a predictable location and orientationwithin the airway 50 lumen.

Another embodiment is shown in FIG. 4. In the embodiment in FIG. 4,catheter 20 includes a plurality of transducers 42, 44, and 46, each ata fixed angle. Because the angles of the transducers are known, the timeof flight ultrasound data can be adjusted to compensate for the angle ofthe pulmonary artery (or other blood vessel) 60 or catheter.Alternatively, the two or more transducers of FIG. 4 may be utilized tocapture Doppler shifted data at more than one angle of incidence to theblood flow. The absolute blood velocity may then be calculated bymathematically eliminating the variable of angle of incidence, as iswell known in the art and described, for example, in U.S. Pat. No.5,339,816.

Another embodiment is shown in FIG. 5. In the embodiment in FIG. 5,catheter 20 is placed flush against the airway wall. Because thetransducer is fixed relative to the catheter, the primary direction ofpropagation of the ultrasound waves is known. As shown, a singletransducer 52 sends signals laterally from the distal section. Thesignals are perpendicular to the direction of fluid flow. Hence, thedirection of the ultrasound waves are in the same direction as thediameter D.

Clearly, any of the above systems can also employ various sensingmechanisms to ensure proper contact of the catheter against an airwaywall (e.g., establishing an electrical circuit, temperature measurement,ultrasound measurement, etc.)

Another embodiment, not shown, includes a single transducer in thedistal section of the catheter. The catheter end section, or transduceritself, is rotated or moved. Information at each location and angle isrecorded. A comparison of the sensed information identifies a range ofpotential dimensions of the diameter. An estimate may then be made inview of the range. For example, the mean may be taken as the closestvalue to the actual diameter. Or, a weighted average may be made. Anexample of a rotation technique is described in U.S. Pat. No. 5,623,930.

Another approach for determining flowrate (Q) includes evaluatingvelocity profiles over time and across a vessel. Notably, it has beenfound that flowrate may be obtained without directly measuring thecross-sectional area of the vessel. This novel technique is describedbelow.

One embodiment includes providing a pulsed wave ultrasound Doppler probeand pulsed-wave ultrasound Doppler processing unit (e.g. UVP Duo,manufactured by Met-Flow, Laussane, Switzerland). The Doppler probeincludes at least one ultrasound transducer. The Doppler probe isadvanced through an endoscope or bronchoscope towards an intra-bronchialsite in either the right or left main bronchus, preferably at a position0-20 mm distal to the carina.

The ultrasound transducer is positioned such that its beam is directedat an angle other than perpendicular to the axis of the vessel (a beamdirected exactly 90 degrees would fail to detect a Doppler shift). Thebeam width is preferably less than the blood vessel diameter.

Referring to FIG. 6, a pulsed wave ultrasound Doppler probe 100 involvessending an ultrasound beam 110 across a blood vessel 120. Analysis ofreflected ultrasound energy is performed by a signal processor (notshown) of sample volumes 130 positioned sequentially along the path ofthe ultrasound beam. Preferably at least two, and more preferably atleast 3 sampling volumes ought to be positioned along the blood vesseldiameter. Stated another way, the length of the sampling volume ispreferably less than ½ of the vessel diameter. Non-limiting examples ofsample volume length range from about 1 to 3 mm, or less.

In this embodiment, the sampling range (i.e. the distance over which thesampling volumes extend along the beam axis) is greater than the bloodvessel diameter, and includes sampling volumes outside the blood vessel.Preferably, the range of sample volumes extends beyond both sides of theblood vessel—from the near or proximal side of the blood vessel, and tothe far or distal side of the blood vessel relative to the Dopplertransducer. In certain cases in which the flow profile is symmetricalabout the vessel axis this method may also be utilized successfullywhere the range extends from some position within the blood vessel thatis proximal to the center of the blood vessel to some position outsidethe blood vessel, distally. Similarly, the method can be utilizedsuccessfully where the range extends from some position proximal to theblood vessel to some position within the blood vessel that is distal tothe center of the blood vessel. A non-limiting example of a samplingrange includes at least 2 mm and more preferably between about 2 and 20mm.

A temporal sampling rate is a rate to collect a plurality ofinstantaneous velocity profiles within a period of time. An illustrationof a velocity profile is shown in FIG. 7, and corresponds to the set upshown in FIG. 6. The temporal sampling rate is preferably great enoughto collect a sufficient number of instantaneous velocity profiles duringeach cardiac cycle, such that the time-averaged volume flow from theseprofiles is an accurate estimate of real volume flow. The temporalsampling rate is preferably at least twice (2×) that of the heart rateand is preferably as great as practicable so that the time variation ofthe flow velocity can be resolved within a heart beat and from heartbeat to heart beat. Human heart rates are typically 60 to 120 beats perminute or 1-2 Hz. A non-limiting example sampling rate is between 5 and20 samples/second.

The sampling period is the time to collect one sample velocity profile.The sampling period is the inverse of the sampling rate. Non-limitingexamples of the sampling period is between 0.05 to 0.2 seconds/sample.

The sampling duration is the length of time during which sequentialvelocity profiles are captured and stored. It is preferably at least aslong as a single heart beat and preferably is at least as long asseveral heartbeats.

The preferred time duration for sampling will be a function of thestability (i.e. repeatability) of the flow characteristics of the heartbeat. For example, in the case of regular heart beat, a time duration offewer than 10 consecutive heart beats is adequate. Nonlimiting examplesof a time duration is between 2 and 20 seconds and more preferablybetween 6 and 10 seconds.

In an application, a large blood vessel is located by probing thebronchial airway walls with an ultrasound Doppler probe. A fluidvelocity profile is continuously monitored using a Doppler processingunit. The fluid velocity profile may be shown on a display. An adjacentblood vessel is indicated by the observation of a time varying velocitywaveform with a typical oscillating flow waveform, characteristic ofpulsatile flow in a blood vessel. Confirmation is accomplished byobserving the velocity curve with a central peak that decays spatiallyto approximately zero over a span of several millimeters. An example ofsuch a velocity waveform with central peak is shown in FIG. 7. Thevelocity profile may consist wholly or in part of one or more negativeflow regions. Negative flow, as defined here, corresponds to flowreversal with respect to positive flow. Flow reversal is typical of thetemporal flow pattern of an artery within a living body, as is wellknown in the art. The designations “positive” and “negative” flow, asdepicted herein, will be understood to depend upon the orientation ofthe ultrasound probe relative to the blood vessel under measurement.

Once the blood vessel to be monitored has been located, theinstantaneous volume flow rate q(t) is determined. Instantaneous volumeflow rate is determined by measuring and summing a plurality of flowrates (e.g., Vol_(N) of FIG. 9a ) across discrete area cross sections ofthe blood vessel. The approximate center of the blood vessel iscomputationally determined by examination of the instantaneous velocityprofile data—the locations of peak velocities for several profiles areaveraged to approximate the center of the blood vessel.

Velocity at positions along the diameter of the vessel are detectedusing Doppler shift measurements, adjusted to account for the angle ofthe Doppler probe relative to the normal vector to the vessel. Asillustrated in FIG. 8, the velocity of fluid traveling axially is equalto v′/sin(theta), where v′ is the velocity measured along the angletheta. Theta may be determined as set forth above, or for example, asdescribed in U.S. Pat. No. 4,103,679 (e.g., see column 4, lines 35-60),which is incorporated by reference in its entirety.

The calculation of instantaneous volume flow rate q(t) is iterative. Tostart the calculation, a first diameter is assumed—this may be equal tothe length of one or two sample volume lengths (e.g., about 0.1 to 2mm). This first diameter d₀ is centered over the approximate bloodvessel axis (e.g., the spatial location where the velocity is highest)and is equal to the adjusted length of one or two pulsed wave ultrasoundDoppler sampling volumes. Volumetric flow is calculated across thiscircular area defined by the following formula:q ₀(t)=u ₀*pi*d ₀ ²/4

-   -   where    -   q₀(t)=instantaneous volume flow rate across a defined circular        area,    -   u₀=measured fluid velocity across defined circular cross        section, and    -   d₀=assumed diameter.

The instantaneous volume flow is then calculated by adding the volumeflow calculations across successively larger annular areas, according tothe following:q _(n)(t)=q ₀ +Σu _(n)*pi*(d _(n) ² −d ² _(n−1))/4

The velocity u_(n) is the average of the velocities of the multiplesampling volumes that cross the annular area for each iteration n (seeFIGS. 9a and 9b ). This summation continues until subsequentcalculations of q_(n)(t) no longer increase or the rate of increase isbelow a pre-determined threshold, indicating that the Doppler samplingvolumes are no longer within the vessel of interest. The value ofq_(n)(t) calculated in the last iteration is the instantaneous volumeflowrate, q(t), calculated without the need to directly measure vesseldiameter.

Volume flowrate calculated in this manner is accurate and free of errorsassociated with poor estimates of vessel diameter, or temporalvariations in vessel diameter that are known to occur due to thecompliant nature of arteries and veins. The number of iterationsnecessary in this step is determined by the mathematical convergence ofq(t). Because the velocity profile within a blood vessel tends towardszero at the blood vessel walls, the contribution of the velocity ringsto the calculation of volumetric flowrate is less for the peripheralrings and more for the central rings. Thus, as the calculation proceedsfrom the center to the periphery of the blood vessel, the value of thecalculated volumetric flow rate will be seen to change more slowly asthe inner edge of the blood vessel is approached. This provides a meansof automatically identifying the diametric limits of the blood vesseland improves the accuracy of the calculation. Accuracy is furtherimproved as the Doppler sampling volume is decreased.

Calculation of Time-Averaged Volume Flow Rate Q.

The time-averaged volume flow, calculated over several instantaneousvelocity profiles within a heart beat and over the course of multipleheartbeats, yields an estimate of the net forward volume flow throughthe blood vessel. This time-averaged flow is described analytically asfollows:

where

$Q = {\frac{1}{\tau}{\int_{0}^{\tau}{{q(t)}d\; t}}}$Q = time-averaged  volume  flow  rate, and τ = sampling  period.

The analytical expression for volume flow rate Q, shown above, can bediscretized for the estimation of volume flow from distinct digitizedvelocity profiles collected, for example, with a pulsed-wave ultrasoundvelocity probe. Velocity profiles can be measured at intervals of Δt,over a sampling period τ. The resulting estimate of average volume flowrate during the sampling period τ then becomes:

τ/Δ t $Q = {\Delta\;{t/\tau}{\sum\limits^{\;}{{q(t)}\Delta\; t}}}$ n = 0

For completeness the following is a combination of previous expressionsand is the formula for volume flow estimation by the described method:

τ/Δ t$Q = {\Delta\;{t/\tau}{\sum\limits^{\;}{\left( {q_{0} + {\sum\limits^{\;}{u_{n}*{pi}*{\left( {d_{n}^{2} - d_{n - 1}^{2}} \right)/4}}}} \right)\Delta\; t}}}$n = 0

The iterative calculation described above is preferably performed byautomated computer processing of pulsed wave Doppler velocity data.

FIG. 10 shows sequential velocity profiles captured during a samplingperiod in a canine blood vessel. The example data was obtained bycollecting velocity profiles in a canine pulmonary blood vessel at atemporal sampling rate of approximately 7 Hz. The Doppler probe systemused was a MetFlow UVP Duo with TX-8 transducer, Lausanne, Switzerland.In particular, a transbronchial catheter was advanced into an airway inthe vicinity of the right branch of the pulmonary artery in the dog.This artery is typically 6-8 mm in diameter in a dog. Velocity data wasthen detected using the pulsed wave ultrasound probe.

It is noteworthy in FIG. 10 that the instantaneous velocity profilesvary within a heartbeat, as would be expected as the blood flow surgesand then subsides and finally reverses within the different sub-stagesof the heartbeat. The measurements are therefore preferably carried outover an extended time duration in order to obtain a time averagedflowrate representative of the net volume flowrate through the bloodvessel. As discussed above, suitable time durations range from 6-10seconds, or longer.

FIG. 11 shows two time-averaged volume flowrate lines. The linesrepresent time-averaged volume flowrates using different diameterthresholds as referred to in Section [0070]. The dashed line correspondsto an calculated maximum diameter of 8.9 mm, and the solid linecorresponds to a calculated maximum diameter was 7.4 mm. Q(t) wascalculated, as described above, namely, by adding component annularvolume flowrates together. As shown, both lines converge to a nearlyconstant value after approximately 10 cardiac cycles (i.e. afterapproximately 6 seconds of data collection), indicating that a diameterof 8.9 mm does not subtend any additional flow and is therefore beyondthe vessel wall; and that 7.4 mm is a correct representation of thevessel diameter. The data shown in FIG. 11 is uncalibrated, so thesteady-state volume “flow rate is not expected to be physiologic.However, calibration is a well known exercise to those having skill inthe art.

FIG. 11, and in particular, the clear convergence of the two lines,suggests that so long as the sampling range spans the vessel and extendsto the zero velocity regions along the edge of the vessel (or beyond),the present invention provides an estimate of the average flowrateregardless of the diameter of the vessel. Thus, so long as theconditions described above are met, and the iterative calculation forq(t) proceeds to a diameter greater than the vessel of interest, anaccurate volume flowrate can be estimated.

Estimation of Cardiac Output.

Cardiac output may be estimated in accordance with the presentinvention. The right and left main pulmonary arteries are bothpositioned anatomically adjacent to the right and left main bronchi.Thus, by probing both of these arteries and summing the resulting bloodvolume flows, one will obtain an estimate of cardiac output. One canalso obtain an estimate of cardiac output by probing one or the other ofthe right or left pulmonary arteries and doubling the blood volume flowfrom that artery. This latter method relies on the assumption thatcardiac output blood volume flow is distributed equally to the right andleft pulmonary arteries. After calibration of the system, it is expectedthat the invention would accurately estimate cardiac output in humansubjects, with measurements in the physiological range of 1-10 litersper minute.

All patents, applications, and publications referenced above are herebyincorporated by reference in their entirety.

What is claimed is:
 1. A method comprising: positioning a transbronchialcatheter inside an airway of a lung of a patient; sending ultrasonicwaves from the transbronchial catheter toward a pulmonary artery of apatient; receiving ultrasonic waves from at least one ultrasoundtransducer of the transbronchial catheter, the at least one ultrasoundtransducer being functionally coupled to a wall of the airway, whereinthe received ultrasonic waves passed through at least one portion of thepulmonary artery without using heart catheterization; determining ameasured pulmonary pressure value by electronically processing theultrasonic waves received from the at least one ultrasound transducer ofthe transbronchial catheter, the received ultrasonic waves having passedthrough the at least one portion of the pulmonary artery; and providingan electronically processed comparison of the measured pulmonarypressure value with a database of a plurality of predetermined pulmonarypressure values to determine whether pulmonary hypertension isindicated, wherein the plurality of predetermined pulmonary pressurevalues comprise baseline measurements of other patients obtained usingheart catheterization, wherein the determination of whether pulmonaryhypertension is indicated is outputted as visual information to anoperator of the transbronchial catheter.
 2. The method of claim 1,wherein each of the plurality of predetermined pressure values isassociated with a mean pulmonary arterial pressure value.
 3. The methodof claim 1, wherein the ultrasonic waves are received from a pluralityof ultrasound transducers of the transbronchial catheter.
 4. The methodof claim 1, wherein measured pressure value comprises a flow-ratewaveform.
 5. The method of claim 1, wherein the plurality ofpredetermined pressure values comprise baseline waveforms collectedusing a known process for determining mean pulmonary arterial pressure.6. A system for evaluating pulmonary circulation information of apulmonary artery of a patient, the system comprising: a transbronchialcatheter that sends and receives ultrasonic waves; a memory that storesa data set of predetermined pulmonary pressure values obtained by directmeasurement of pulmonary arterial pressure; a microprocessor coupledwith the transbronchial catheter and with the memory storing the dataset of predetermined pulmonary pressure values, the microprocessor beingconfigured to: receive a signal associated with detected ultrasonicwaves from at least one ultrasound transducer of the transbronchialcatheter positioned inside an airway of a lung of a patient, when the atleast one ultrasound transducer is functionally coupled to a wall of theairway of the lung, wherein the received signal is associated withultrasonic waves passed through at least a portion of the pulmonaryartery without using heart catheterization; determine a measuredpulmonary pressure value by electronically processing the receivedultrasonic waves; and provide a comparison by electronically processingthe measured pressure value with the data set of predetermined pulmonarypressure values that comprise baseline measurements of other patientsusing heart catheterization; and a visual indicator or display coupledto the microprocessor, wherein the microprocessor is configured tooutput visual information related to the comparison to the visualindicator or display.
 7. The processing unit of claim 6, wherein themicroprocessor is configured for performing Doppler ultrasound analysisto the received ultrasonic waves to determine the measured pressurevalue.
 8. The processing unit of claim 6, wherein the data set ofpredetermined pressure values comprise baseline waveforms collectedusing a known process for determining mean pulmonary arterial pressure.